The primary goal of this award application is to allow me to develop the skill and knowledge necessary to establish a successful independent research program in the development of the auditory system and hearing rehabilitation. As an otolaryngologist, I am keenly aware of the impact of hearing loss on the lives of my patients. Because hearing loss directly affects the ability of people to communicate, these impacts can be far reaching. Although I have an extensive background in basic science research, I have only recently entered the auditory field. In addition, during my medical school years and residency, the time that I was able to devote to research was limited by clinical responsibilities. The training period supported by this award will allow me to become knowledgeable and proficient in the field of auditory neuroscience. An outstanding group of scientists has agreed to assist me in this process. This time will also enable me to broaden my understanding of limitations with current modalities of treatment of hearing loss, including cochlear implantation, middle ear hearing aids and reconstructive middle ear surgery. It is my expectation that this training period will enable me to establish the foundation for an innovative research program in auditory development and give me insight into new strategies for the treatment of hearing loss. Auditory perception is encoded by neural circuits that interconnect hair cells in the inner ear and the central nervous system. The assembly of this exquisitely ordered network is dependent on the precise arrangement of multiple cell types in the inner ear and the establishment of accurate axonal projections to the cochlea during embryogenesis. The Iong-term, goal of this research program is to identify the molecular signals that regulate the specification of hair cells and their synaptic connections during development and use these signals to design strategies to treat human hearing loss. In this proposal, I have outlined a series of experiments to characterize the normal developmental process of hair cell innervation. I will then utilize an in vitro culture system to test the ability of postnatal auditory neurons to innervate new hair cells, a model of regeneration. Finally, I will use molecular techniques to begin to dissect the signals that regulate axon guidance in the developing auditory system.
| Luo, Chuan; Omelchenko, Irina; Manson, Robert et al. (2015) Direct Intracochlear Acoustic Stimulation Using a PZT Microactuator. Trends Hear 19: |
| Lewis, Rebecca M; Hume, Clifford R; Stone, Jennifer S (2012) Atoh1 expression and function during auditory hair cell regeneration in post-hatch chickens. Hear Res 289:74-85 |
| Golub, Justin S; Tong, Ling; Ngyuen, Tot B et al. (2012) Hair cell replacement in adult mouse utricles after targeted ablation of hair cells with diphtheria toxin. J Neurosci 32:15093-105 |
| Atkinson, Patrick J; Wise, Andrew K; Flynn, Brianna O et al. (2012) Neurotrophin gene therapy for sustained neural preservation after deafness. PLoS One 7:e52338 |
| Wise, Andrew K; Tu, Tian; Atkinson, Patrick J et al. (2011) The effect of deafness duration on neurotrophin gene therapy for spiral ganglion neuron protection. Hear Res 278:69-76 |
| Lin, Vincent; Golub, Justin S; Nguyen, Tot Bui et al. (2011) Inhibition of Notch activity promotes nonmitotic regeneration of hair cells in the adult mouse utricles. J Neurosci 31:15329-39 |
| Wise, Andrew K; Hume, Clifford R; Flynn, Brianna O et al. (2010) Effects of localized neurotrophin gene expression on spiral ganglion neuron resprouting in the deafened cochlea. Mol Ther 18:1111-22 |
| Hume, Clifford R; Bratt, Debra Lee; Oesterle, Elizabeth C (2007) Expression of LHX3 and SOX2 during mouse inner ear development. Gene Expr Patterns 7:798-807 |
| Bermingham-McDonogh, Olivia; Oesterle, Elizabeth C; Stone, Jennifer S et al. (2006) Expression of Prox1 during mouse cochlear development. J Comp Neurol 496:172-86 |
